The lymphoid lineage–specific actin-uncapping protein Rltpr is essential for costimulation via CD28 and the development of regulatory T cells

Yinming Liang, Margot Cucchetti, Romain Roncagalli, Tadashi Yokosuka, Aurelie Malzac, Elodie Bertosio, Jean Imbert, Isaac Nijman, Miloslav Suchanek, Takashi Saito, Christoph Wülfing, Bernard Malissen, Marie Malissen

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Abstract

Although T cell activation can result from T cell antigen receptor (TCR) signals alone, physiological T cell responses require CD28 costimulation. Using an N-ethyl-N-nitrosourea- mutagenesis screen, we identified a mutation in the Rltpr gene. We demonstrated that Rltpr is a lymphoid cell-specific, actin-uncapping protein essential for CD28 costimulation and regulatory T cell development. TCR-CD28 engagement at the immune synapse resulted in the colocalization of CD28 with both wild-type and mutant Rltpr forms. However, the connection between CD28 and protein kinase C-θ and Carma1, two key effectors of CD28 costimulation, was abrogated in T cells with the Rltpr mutation and CD28 costimulation did not occur. Our findings provide a more complete model of CD28 costimulation in which Rltpr plays a key role.
Original languageEnglish
Article numberdoi:10.1038/ni.2634
JournalNature Immunology
Early online date23 Jun 2013
DOIs
Publication statusPublished - 2013

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    Liang, Y., Cucchetti, M., Roncagalli, R., Yokosuka, T., Malzac, A., Bertosio, E., Imbert, J., Nijman, I., Suchanek, M., Saito, T., Wülfing, C., Malissen, B., & Malissen, M. (2013). The lymphoid lineage–specific actin-uncapping protein Rltpr is essential for costimulation via CD28 and the development of regulatory T cells. Nature Immunology, [doi:10.1038/ni.2634]. https://doi.org/doi:10.1038/ni.2634